In recent years, there has been a significant amount of media attention on the subject of food allergy. While the exact prevalence is unknown, recent estimates suggest that 6% of young children and up to 4% of adults in North America are affected by food allergy, and the prevalence of the disorder appears to be rising [1–4].

Food allergy is also a leading cause of anaphylaxis (a severe, potentially fatal allergic reaction; please see Anaphylaxis article in this supplement for more information) presenting to emergency departments [2]. Annually, there are approximately 200 deaths in the United States attributed to food allergy [5]. At present, there are no accurate data regarding food allergy-related deaths in Canada.

Accurate diagnosis and appropriate management of food allergy are critical since accidental exposure to even minute quantities of the food causing the allergic reaction may result in anaphylaxis [6]. This article provides an overview of current literature related to the epidemiology, pathophysiology, diagnosis, and appropriate management of food allergy. This review focuses primarily on immunoglobulin E (IgE)-mediated food-allergic reactions.

The term food allergy is used to describe an adverse immunologic response to a food protein. It is important to distinguish food allergy from other non-immune-mediated adverse reactions to foods, particularly since more than 20% of adults and children alter their diets due to perceived food allergy [4]. Adverse reactions that are not classified as food allergy include food intolerances secondary to metabolic disorders (e.g., lactose intolerance), reactions to toxic contaminants (e.g. histamine produced by scombroid fish contaminated by Salmonella organisms) or pharmacologically active food components (e.g. caffeine in coffee causing jitteriness, tyramine in aged cheeses triggering migraine). Other conditions which are associated with symptoms similar to food allergy include auriculotemporal syndrome (a disorder characterized by facial flushing and salivation that may follow trauma to the parotid gland), and gustatory rhinitis [2–4].

Although food allergy can arise to any food, the allergens responsible for more than 85% of food allergy are: milk, egg, peanut, tree nuts, shellfish, fish, wheat, sesame seed and soy [5]. These are also the “priority” allergens defined by Health Canada. It is the protein component, not the fat or carbohydrate component, of these foods that leads to sensitization and allergy. The allergenic segments or “epitopes” of these proteins tend to be small (10 to 70 kd in size), water-soluble glycoproteins that are generally resistant to denaturation by heat or acid and, therefore, can remain intact even after processing, storage, cooking and digestion [3, 4, 6]. Examples of these glycoproteins include caseins in milk, vicillins in peanut, and ovomucoid in egg. In general, allergies to additives and preservatives are uncommon.

Food-induced allergic disorders are broadly categorized into those mediated by immunoglobulin E (IgE) antibodies or by non-IgE-mediated mechanisms. IgE-mediated allergic responses are the most widely recognized form of food allergy and are characterized by the rapid onset of symptoms after ingestion. During initial “sensitization” to the food, consumption of the allergenic food protein stimulates production of IgE antibodies specific to that food which then bind to tissue basophils and mast cells. When the causal foods are subsequently eaten, they bind to their specific IgE antibodies and trigger the release of mediators, such as histamine, prostaglandins and leukotrienes, causing “clinical reactivity” and allergic symptoms. It is important to note that sensitization can be present without clinical reactivity, meaning that specific IgE to a food is present, but no reaction occurs with exposure [2–4, 7, 8].

Non-IgE-mediated (cell-mediated) food allergy is less common and results from the generation of T cells that respond directly to the protein, leading to the release of mediators that direct certain inflammatory responses (e.g., eosinophilic inflammation) and can cause a variety of subacute and chronic disease states. These types of reactions typically affect the gastrointestinal (GI) tract and skin and include: dietary-protein-induced enterocolitis and proctitis, celiac disease and its related skin disorder dermatitis herpetiformis. Celiac disease is associated with a specific immunoglobulin A (IgA)-mediated sensitivity to gluten (a protein found in wheat, barley, rye and certain other grains), and is associated with chronic inflammation and damage to the villi of the small intestine. Dermatitis herpetiformis is a chronic skin disorder that may occur simultaneously with celiac disease or alone [2–4, 7].

Some disorders are associated with a mixed IgE-/cell-mediated pathophysiology to food, such as atopic dermatitis, eosinophilic gastroenteritis and eosinophilic esophagitis (EoE; see articles on EoE and atopic dermatitis in this supplement). In these disorders, the association with food may not be demonstrated in all patients.

The spectrum of food-allergy-associated disorders according to pathophysiology is shown in Figure 1. It is important to note that food allergy is not a cause of conditions such as migraines, behavioural or developmental disorders, arthritis, seizures or inflammatory bowel disease.

Children with atopic disorders tend to have a higher prevalence of food allergy; approximately 35% of children with moderate-to-severe atopic dermatitis have IgE-mediated food allergy [12]. Studies have also shown that children with atopic dermatitis and food allergy have a higher prevalence of allergic rhinitis and asthma. Approximately 75% of children with atopic dermatitis develop allergic rhinitis and 80% develop asthma [13].

Skin reactions are the most common clinical manifestations of allergic reactions to food and include acute urticaria (hives), angioedema (swelling) and erythema (redness of the skin). Typical respiratory tract symptoms include laryngeal edema, rhinorrhea, and bronchospasm. GI-related signs and symptoms of food allergy include nausea, vomiting, abdominal pain, and diarrhea.

The diagnosis of a food allergy requires a detailed history and physical examination, and diagnostic tests, such as skin prick tests (SPT) and/or serum-specific IgE testing to foods (ImmunoCAP^®). In some cases, oral food challenges may also be required [2–4].

Referral to an allergist is important to confirm the diagnosis of a suspected food allergy. Patients should avoid the food in question until assessment, and an epinephrine auto-injector should be prescribed, even if the diagnosis is uncertain [6].

There is currently no treatment for food allergy, beyond avoidance of the responsible food(s). Once a food allergy is diagnosed, strict elimination of the offending food allergen from the diet is necessary. A properly managed, well-balanced elimination diet can lead to resolution of symptoms while maintaining nutritional status. When the elimination diet is used as treatment, the identified food allergens are removed from the diet indefinitely, unless evidence exists that the food allergy has resolved [2–4].

In the case of accidental exposure, the treatment of choice is epinephrine administered by intramuscular injection into the lateral thigh [2–4]. There are currently two epinephrine auto-injectors available in North America: EpiPen^® and Twinject^®. Both products come in two dosages (0.15 mg and 0.30 mg), which are prescribed according to weight. The 0.30 mg dosage should be used for those weighing 30 kg or more, and the 0.15 mg dosage for children weighing between 15–30 kg. Certain sources recommend switching to the 0.30 mg dose at 25 kg rather than 30 kg [19].

These devices should be stored properly (avoiding temperature extremes) and replaced before the expiration date. More information on these auto-injectors is available at http://www.epipen.ca and http://www.twinject.ca. All individuals receiving emergency epinephrine must be transported to hospital immediately (ideally by ambulance) for evaluation and observation [20].

A concise, written plan for the treatment of allergic reactions resulting from accidental exposure to the food should be developed, and copies made available to the appropriate persons (e.g., daycare providers, teachers, employers). Examples of such a plan, along with other relevant information and materials, can be downloaded at Anaphylaxis Canada (http://www.anaphylaxis.ca) or the Food Allergy and Anaphylaxis Network (http://www.foodallergy.org; a US-based association). Recommendations for the management of anaphylaxis in schools and other community settings [20] are also available through the Allergy Safe Communities website at http://www.allergysafecommunities.ca.

Patients and their caregivers must also be educated on food avoidance, the identification and treatment of allergic and anaphylactic reactions, the appropriate use of epinephrine auto-injectors, and how to obtain immediate medical assistance (e.g., call 911) (see Anaphylaxis article in this supplement for more information). Individuals should also be instructed to read food labels carefully, watching for hidden ingredients such as “natural flavour” or “spices” that may indicate the presence of allergens, as well as “may contain” warnings. All food-allergic patients should obtain and wear medical identification (such as a MedicAlert® bracelet/necklace) indicating their food allergy [6].

Recent research has also shown that peanut allergic children can be desensitized to peanut by feeding them increasing amounts of peanut under close supervision [21]. Similar studies have been conducted for egg and milk allergy. Results of these studies are promising; however, they have involved only small numbers of subjects, side effects have been noted, and protocols are still evolving. Therefore, further confirmatory studies in this area are needed.

A simplified algorithm for the diagnosis and management of food allergy is provided in Figure 2.

Strategies for the prevention of food allergy have been extensively studied. Prior recommendations suggesting avoidance of highly allergenic foods in infant diets and the diets of pregnant/breastfeeding mothers have not been shown to decrease the prevalence of food allergy or atopic disease [6]. Recent guidelines from the American Academy of Pediatrics state that “no current convincing evidence exists to recommend specific avoidance of certain foods beyond 4-6 months of age for the prevention of allergy” [22].

The prognosis of food allergy is complex and dependent on the particular food. As mentioned earlier, most infants and young children outgrow allergies to milk, egg, soy and wheat. Children should be re-evaluated at regular intervals to determine whether clinical tolerance has developed. The natural history of egg and milk allergy appears to be evolving in that an increasing number of children are outgrowing these allergies in their teenaged years [23, 24]. Allergy to peanut, tree nuts, fish, and shellfish is more persistent, and lifelong in most cases.

Food allergy is an important clinical problem of increasing prevalence. Assessment by an allergist is very important for appropriate diagnosis and treatment. Diagnosis currently relies on a careful history and diagnostic tests, such as SPT, serum-specific IgE testing (where appropriate) and, if indicated, oral food challenges. The mainstay of treatment is avoidance of the responsible food(s) and appropriate, prompt response to allergic reactions with epinephrine. Further insights into the pathophysiology of food allergy will lead to the development of improved methods for prevention, diagnosis, and management of the disorder.